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Kinetics of negative and positive selection in the thymus
1Basel Institute for Immunology, Switzerland.
Recent experiments show that CD4+8+ thymocytes represent the critical stage in T cell development at which the specificity of randomly generated alpha beta T cell receptors is screened. These cells are deleted when the receptor binds to the MHC molecule plus specific peptide presented by bone marrow derived cells but are rescued from cell death and induced to mature if the receptor binds to the MHC molecule on thymic epithelium in the absence of the specific peptide. Different tolerogens delete CD4+8+ thymocytes earlier or later during their lifespan and negative selection can occur prior to positive selection. The specificity of the alpha beta T cell receptor for either class I or class II thymic MHC molecules determines the CD4-8+ and CD4+8- phenotype of mature T cells.
Recent experiments show that CD4+8+ thymocytes represent the critical stage in T cell development at which the specificity of randomly generated alpha beta T cell receptors is screened. These cells are deleted when the receptor binds to the MHC molecule plus specific peptide presented by bone marrow derived cells but are rescued from cell death and induced to mature if the receptor binds to the MHC molecule on thymic epithelium in the absence of the specific peptide. Different tolerogens delete CD4+8+ thymocytes earlier or later during their lifespan and negative selection can occur prior to positive selection. The specificity of the alpha beta T cell receptor for either class I or class II thymic MHC molecules determines the CD4-8+ and CD4+8- phenotype of mature T cells.